Polymerase Theta (Polθ) is our leading pre-clinical program.
We are developing a small molecule inhibitor of polymerase theta, or Polθ, a SL target associated with BRCA mutations and other genomic alterations. This program was added to our portfolio through a collaboration with our co-founder, Dr. Agnel Sfeir at Memorial Sloan Kettering Cancer Center, who initially published her observations on the SL between BRCA and Polθ in Nature in 2016.
Polθ is a DNA polymerase enzyme that participates in the repair of double-strand breaks in DNA. Mutations in genes such as BRCA1 and BRCA2 increase the frequency of these breaks, resulting in SL with Polθ. Preclinical studies have shown that inactivation of Polθ, both on its own and in combination with PARP inhibitors, reduces survival in BRCA-mutated cells, but not in BRCA wild-type cells. BRCA1 and BRCA2 mutations are routinely identified in multiple genetic profiling tests and observed in approximately 1% to 7% of patients with breast and ovarian cancer.
Polθ is one of the most exciting new targets in DNA damage repair identified in recent years.
We anticipate advancing a development candidate and initiating IND-enabling studies for this program in the first half of 2022.